One of Little Italy’s longest-operating restaurants was damaged on Saturday by an early-morning fire that seriously injured two people and left 11 others with minor injuries, the New York City Fire Department said.

Angelo’s of Mulberry St., at 146 Mulberry St., has served Neapolitan cuisine since 1902, according to its website. Photographs show that politicians and celebrities who have eaten there include President Ronald Reagan and the basketball star Kobe Bryant.

The call about the fire came in at 7:41 a.m. through the city’s 911 system, said Kenneth Reilly, a spokesman for the Fire Department. Firefighters arrived to find the first two floors of the six-story building engulfed in flames. Residential apartments sit above the ground-floor commercial unit.

The fire quickly generated a second alarm and 25 fire trucks and 106 firefighters arrived at the scene. The blaze was declared under control at 9:20 a.m., Mr. Reilly said.

Five people were transported to the hospital, including the two people with serious injuries. A firefighter was among three people taken to the hospital with minor injuries.

The Buildings Department is examining the structure and the fire marshal will determine the cause of the fire, which remains unknown, Mr. Reilly said.

Matthew Teter, a spokesman for the Red Cross of Greater New York, said people from three apartments on the second and third floors had been offered housing assistance because their apartments were destroyed. They were able to make other arrangements, he added.

Joseph V. Scelsa, the founder and president of the Italian American Museum, said Angelo’s was the oldest restaurant in Little Italy.

“It’s a landmark. I have people that come to the neighborhood who go to the museum and make it a pilgrimage to go there,” Mr. Scelsa said. “The food was excellent. People who came back who knew the neighborhood would always go there.”

Workers from the restaurant sat in the museum, which is close by, as emergency responders worked at the scene, Mr. Scelsa said.

“Like so many of these older places, if they get destroyed like this, it takes a lot to bring them back,” Mr. Scelsa said. “We are losing so many of the old places.”

Marci Todd, the office manager for Tramonti, a Delray Beach, Fla., restaurant that is referred to as Angelo’s “sister” restaurant on its website, said the family that owns Angelo’s was too distraught to speak with reporters.

The restaurant has operated in the same location since 1902, she said.

“Everybody is just in shock right now,” Ms. Todd said in a phone interview. “You have a restaurant that long, have it be successful, and it’s gone in a matter of minutes.”